Rearrangement of aminocycloalkanone oximes to the corresponding lactams

ABSTRACT

Alpha -amino- delta -valerolactam and Alpha -amino- Epsilon caprolactam are produced by contacting the corresponding Alpha aminocycloalkanone oxime or mineral acid salt thereof with liquid SO2 containing at least about 1 mole SO3 per mole Alpha aminocycloalkanone oxime until a two-phase system comprising a liquid SO2 phase and an insoluble lactam precursor phase is formed; separating the liquid SO2 phase from the insoluble phase containing the lactam precursor; hydrolyzing and neutralizing the insoluble lactam precursor phase and recovering the free lactam product.

United States Patent 1191 Fuhrmann et a1.

1 1 REARRANGEMENT OF AMINOCYCLOALKANONE OXIMES TO THE CORRESPONDING LACTAMS [75] Inventors: Robert Fuhrmann, Morris Plains;

Allen A. Tunick, Denville; Stylianos Sifniades, Madison. all of NJ.

[73] Assignee: Allied Chemical Corporation, New

York. N.Y.

[22] Filed: Jan. 16, 1974 [21] Appl. No.: 433,967

[52] U.S. Cl. 260/239.3 R; 260/293.86 [51] Int. Cl. C071) 223/10; CO7D 211/76 [58] Field of Search ..260/239.3 A, 293.86,

[56] References Cited UNITED STATES PATENTS Blaser et a1. 260/2393 A Blaser et a1. 260/2393 A 1 1 Nov. 25, 1975 Well. 260/2393 A Ito et a1. 260/2393 A Primary E.raminerHenry R. Jiles Assistant Examiner--Robert T. Bond Attorney, Agent, or Firm-Arthur J. Plantamura; Ellen T. Dec

[5 7] ABSTRACT tralizing the insoluble lactam precursor phase and recovering the free lactam product.

8 Claims, No Drawings REARRANGEMENT OF AMINOCYCLOALKANONE OXIMES TO THE CORRESPONDING LACTAMS FIELD OF THE INVENTION This invention is directed to the Beckmann Rearrangement of a-aminocyclopentanone and a-aminocyclohexanone oximes to the corresponding ozamino-wlactams using S in liquid S0 as the reagent.

DESCRIPTION OF THE PRIOR ART The Beckmann rearrangement of cycloalkanone oximes and their salts to produce the corresponding lactams using traditional Beckmann rearrangement agents is a conventional technique. Since unsubstituted alicyclic ketoximes have a symmetrical structure, the Beckmann rearrangement mechanism can lead to only one product, i.e.

o 5 g CH\2 CH2 H c11 CH2 (CH \(cafl HO-N is no way to predict what other reagents would cause the formation of such an intermediate.

An alternative Beckmann rearrangement mechanism has been proposed in Japanese Patent 48 10788 involving the use of sulfuric acid containing relatively small amounts of S0 In the first stage of this operation, the anti-aminocyclohexanone oxime is converted to the syn-isomer. In the second stage, the syn-isomer is converted to the lactam without the necessity of formulating the heterocyclic intermediate.

In accordance with the method taught by Ito et al., it is essential that at least two moles of HSO CI, H 50 or S0 per mole oxime be used. Japanese Patent 73 10788 requires the use of at least'4 moles H 80 50;, per mole oxime. Thus, according to both methods, the resulting lactam product is present in the form of a solution in a largeexcess of sulfuric acid containing unreacted 50 or ClSO H. This solution must then be neutralized in order to recover the desired lactam. This neutralization step is usually carried out with ammonia and the rearrangement agent is then recovered as ammonium sulfate. By using these techniques, large quantities, (i.e. considerably more than 5 moles per mole 'lactam) of combined ammonium sulfate and ammonium chloride by-product result. Specifically, a minimum of 6 moles ammonium sulfate and 3 moles ammonium chloride are formed when the chlorosulfonic acid/sulfuric acid system is employed. The formation of these large amounts of NH CI also contaminates the ammonium sulfate by-products after neutralization of the rearrangement mixture and thereby restricts severely its use as a fertilizer. In order to obtain favorable yields of the lactam using the SO /H SO system with ACO-HCI as disclosed by Ito et al., 8 moles ammonium sulfate and 1 mole NH CI are produced.

While the H SO ,/SO system disclosed in the Japanese reference results in the formation of only 1 mole NH CI, at least 4 moles (Nl-I SO are produced.

Moreover, using the rearrangement systems of Ito et al. and of the Japanese reference, the solvents, specifically H SO I-IOS CI, etc., function not only as solvents for the reagents but also as solvents for the lactam H O Nd o N NH H decomposition small N NH 9 products amounts HSO CI used as both reagent and solvent HSO CI dichloroethane SOCl H 50;

It is postulated that the use of these particular combinations by Ito et al. causes formation of a heterocyclic intermediate having a syn-configuration. However, there product. It is thus necessary to perform further complicated operations to remove the lactam from the solution. Thus, since these sulfate-containing reagent systems previously employed have been found to be disadvantageous due to excessive by-product formation and solubility of product, there is a need for other reagents which will give high yields of the corresponding 0:- amino-w-lactam which can be readily recovered in its solid form while resulting in the production of a by-product having widespread commercial usage and containing relatively little ammonium chloride contamination.

SUMMARY OF THE INVENTION In accordance with the procedure of the present invention, it has been found that the use of 50;, in liquid S0 as the Beckmann rearrangement system produces high yields of a-amino-e-caprolactam and a-amino-8- valerolactam. These lactam compounds may be represented by the general formula:

(CH n wherein n is an integer 2 or 3. Moreover, since these reaction products are insoluble in this specific medium, the product may be easily recovered by filtration and the solvent recycled without neutralization. An additional feature of this method is that relatively small amounts (i.e. less than 3 moles) of ammonium sulfate per mole oxime are formed upon neutralization of the reaction mixture and only one mole of the NH ,CI per mole oxime hydrochloride is produced.

This invention is thus directed to a method for the production of a-amino-S-valerolactam and a-amino-ecaprolactam comprising the steps of contacting the corresponding a-aminocycloalkanone oxime or mineral acid salt thereof with liquid sulfur dioxide containing at least about 1 mole sulfur trioxide per mol oxime until the rearrangement is complete and a two-phase system comprising a liquid SO phase and an insoluble lactam precursor phase forms; separating the liquid sulfur dioxide phase from the insoluble phase containing a lactam precursor; hydrolyzing and neutralizing the insoluble lactam precursor phase; and recovering the free lactam product. i

The totally unexpected advantages to the use of S over H 50 as a solvent for the S0 Beckmann reagent may be tentatively explained by the fact that the lower dielectric constant of the SO /S0 system influences the rates of ring closure and rearrangement reactions thereby optiming formation of the postulated syn configuration intermediate, i.e.

CHK ii-NH tcn i I which is readily converted to the postulated lactim compound:

so CH-r-NH This lactim compound is then hydrolyzed to form the desired amino-substituted lactam product in the form of the sulfate salt which is neutralized to produce the free latcm product. The hydrolysis and neutralization the case of amino substituted uctis insoluble in the liquid S0 prior to neutralization."

Accordingly, substantially all the solvent, i.e. the; can be removed from the system by filtration or decanting techniques and this relatively large amount of 80-; need not be subjected to any neutralization'Thus, ac-

cording to the method of the present invention, the :energy expended to neutralization operations as well as I the amount of by-product produced is substantially reduced. in particular, the amount of product which must be neutralized comprises only that produced by the amount of S0,, in the reaction mixture as well as by HCl present in the starting oxime salt and no neutralization V a of solvent is required. Moreover, the removal of liquid S0 solvent by decanting, centrifuging or filtering is far more simple and economical than the flash evaporation of the bulk of the solvent followed by compression of the latter as required in prior Beckmann rearrangement systems using S0 I This method may also be easily adapted to the con-: tinuous production of the amino lactam by simply recy-;

cling the S0 solvent with norequirement to distill or extensively refine the volatile solvent.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The oz-amino-cycloalkanone oximes useful as starting materials in the present invention may be represented by thegeneral formula: 3

NOH

' NH2- CH2 C (c ngh/ where n is a positive integer and may be 2 or 3; These f, oximes may be prepared using conventional methods such as amination of the correspondingchloro-nitroso,1 cycloalkane dimers as disclosed in British Patent No.

1,279,906. Although the oxime may. be used as a free base, higher yields are attained using the'oxime in the. 7 form of a salt with a strong mineral acid such as the. sulfate or phosphate or preferably, the hydrochloride. 1

The Beckmann rearrangement reagent used in our novel process, 80;, in liquid S0 may be readily -obtained by partial catalytic oxidation of S0 followed by condensation of the gaseous S0 and S0 mixture. The S0 should be present in amounts of about 1 to .5 moles, preferably about 1.5 to 2.5 moles 80;, per mole ever, no substantial benefit is known to ensue. a

We have found reaction temperatures of about 25-l 25C preferably about 30-80 to give favorable,

results at pressures of about 3 to 50 atmospheres al though other temperatures and pressure conditions may be employed.

The reaction is preferably carried out by combining the S0,, and the liquid S0 before gradually introducing the a-amino-cycloalkanone oxime or its mineralacid I cyclopentanone andcyclohexanone oximes, the resulting rearrangement prod- 5 salt. Alternatively 50:, may be added to the mixture of a-amino-cycloalkanone oxime and S Since the reaction is exothermic, appropriate cooling means should be incorporated within the system.

Depending upon temperature, reactants, concentrations and other variables, the reaction is complete within less than about 5 hours, generally in 1 to 3 hours. Completion of the reaction can be determined by observing the disappearance of the oxime by thin layer chromotography.

A heterogeneous solid phase separates out of the mixture during the course of the reaction. It is postulated that this solid is the lactam precursor, a-amino-wlactim sulfate, which is insoluble in S0 This precursor phase is readily removed using conventional filtration or decanting techniques. This step can be performed at atmospheric pressure and temperatures below about l0C. or at higher temperatures under suitable pressure conditions. The resulting filtrate or supernatant liquid containing substantially all the S0 solvent is simply recycled. Optionally, a portion of the S0 recycle stream may be purged and sent to a purification process, consisting of distillation from the small amounts of soluble by-products. The remaining insoluble phase containing the solid lactam precursor is then hydrolyzed at about OlOC. to produce the lactam in the form of its sulfate salt and neutralized to yield the free lactam product. This hydrolysis and neutralization may be performed in separate operations but is most conveniently carried out simultaneously using aqueous ammonia, or preferably, an aqueous solution of ammonium sulfate and ammonia. The lactam in the form of the free base is then readily isolated using a variety of methods including solvent extraction and ion exchange procedures. The neutralization by-products are removed and the lactam recovered or further treated in accordance with its ultimate usage.

The resulting lactams can be easily hydrolyzed to produce the corresponding a-aminocarboxylic acids. In particular, a-amino-e-caprolactam can be hydrolyzed with more than2 moles HCl per mole lactam to produce lysine dihydrochloride.

The following examples will-serve to further illustrate this invention.

EXAMPLE 1 A ml (335 mmole) portion of liquid SO- was condensed into a 100 ml aerosol compatibility tube containing an efficient magnetic stirring bar. A 2.0 ml (3.8 g, 48 mmole) sample of liquid S0 was added, and the resulting solution treated at S50C. (external dryice/acetone bath) and with good stirring with 3.29 g mmoles) of Z-aminocyclohexanone oxime hydrochloride (AC O.HCl). The tube'was closed and warmed to 40C., and the temperature maintained for two hours with good stirring. During this period, a second semisolid-liquid phase or viscous solid formed. The mixture was then cooled in dry ice and the tube opened and treated with 15 g. ice. The tube was resealed and warmed to melt the ice and complete hydrolysis. The $0 was then allowed to evaporate, and the residual aqueous solution was neutralized with aqueous ammonia. For the purposes of yield determination, the resulting solution was then placed on a basic ion-exchange column (120 ml Dowex lX-8) and eluted with water.

6 The eluate (500ml) was taken to dryness (rotary evaporator), and the residual oil dissolved in ml. absolute ethanol. The ethanol solution was acidified with a concentrated solution of dry HCl gas in absolute ethanol, and the resulting precipitate of 2-aminocaprolactam hydrochloride (ACL-HCI) collected by filtration and washed with absolute ethanol. After drying in vacuo the yield was 2.20 g (64.6%). The mother liquor and washings were combined and concentrated to afford a second crop weighing 0.08 g. Total yield of pure 2- aminocaprolactam hydrochloride was thus 2.28 g (66.9%).

EXAMPLE 2 To illustrate the simplicity with which the product can be recovered and the fact that the S0 can simply be decanted from the system with no substantial loss of product, the procedure of Example 1 was repeated, however, after the two hour reaction period, the mixture was cooled to 20, the supernatant liquid S0 decanted and the remaining lactim-containing solid phase treated with 15 gm ice water. This lactim mixture was 'then neutralized with sodium hydroxide and the resulting amino-lactam was extracted using glyme as a solvent. After drying the yield obtained was substantially equal to that obtained in Example 1. Little or no product was removed with the decanted S0 as shown by evaporation of the decanted S0 EXAMPLE 3 An illustrative continuous process for the production of a-amino-e-caprolactam is described. Aminocyclohexanone oxime.HCl and S0 were combined with recycled S0 and the mixture was treated as in Example 2. After filtration of the lactim containing phase a portion of the S0 stream was purged to eliminate small amounts of soluble material and combined with the remaining S0 for recycle to the reactor. The solid lactam precursor was contacted with aqueous solution of ammonia and (NH SO to hydrolyze and neutralize the aminocaprolactam precursor thereby producing the aminocaprolactam product. The solution was subjected to partial evaporation to remove any remaining small amounts of S0 and then the-mother liquor containing the a-amino-e-caprolactam was extracted with hot toluene (ca. 70C.). Upon cooling, the a-amino-ecaprolactam crystallized and could be readily separated from the toluene which is then recycled to the extraction step. The portion of the extract containing the EXAMPLE 4 The procedure of Example 2 was repeated using 0:- amino cyclopentanone oxime hydrochloride to produce a-amino-w-valerolactam.

EXAMPLE 5 To show the unique characteristics of the SO /S0 Beckmann reagent system as disclosed herein, the procedure of Example 2 was repeated using other known Beckmann reagents in S0 solvent. The results are shown in Table l.

TABLE] ACO Temp. Time Approx. Approx.

Salt Solvent Catalyst C. hr. Conv'n (7r Yield (71) .HCl 50-; SO- ,CL 35 2 75 trace .HCl 50;, ClSO,,H 44 2 8O 50 Base S POClg 48 2 I00 20 .HCl SO P 0 45 e 2.5 45 .HCl SO PPA (N0! miscible) b. separating the liquid sulfur dioxide phase from the AMPLE 6 insoluble phase containing the lactam precursor; V

The procedure of Example 2 was repeated using varic. hydrolyzing and neutralizing the insoluble lactarn ous reaction proportions, conditions and isolating proprecursor phase; and i I cedures. The results are shown in Table ll. d. recovering the free lactam product. TABLE II Vol. Moles S03 $02 per Temperature Time Isolation Isolated Yield (ml) Mole ACO (C.) (hr.) Procedure ("/e) 2.0 7O cation 61.0

exchange l5 2 0 25-30 4 toluene 56.4

extraction l5 2 2 2 cation 67.4

exchange 30 2.4 2 anion (16.9

exchange l5 2.4 40 2 anion 63.6

exchange 20 2.4 25 4 anion 61.2

exchange 20 2.4 50 2 union 66.0+

exchange 15 14 80 1.2 anion 61.5

exchange 2. The method of claim 1 wherein the lactam precur- I We claim: 35 sor is neutralized and hydrolyzed simultaneously using l. A method for the production of an a-amino-w-lacan aqueous solution of ammonium sulfateand ammov tam of the formula: nia. 1 1

3. The method of claim 1 wherein about 1.5-2.5 moles sulfur trioxide are present per mole a-aminocy- 4O cloalkanone oxime. i H 4. The method of claim 1 wherein about 2m 2 0, 1 f moles sulfur dioxide are present per mole sulfur trioxt CH ide.

(CH 5. The method of claim 1 whereinthe oz-aminocy- I cloalkanone oxime is present in the form of its'hydro- I chloride salt. v wherein n is an integer of 2 or 3, comprising the steps 6. The method of claim 1 wherein the a-aminocyj of: cloalkanone oxime is a-aminocyclohexanone oxime.

a. contacting the corresponding a-aminocycloalka- 7. The method of claim 1 wherein the reaction tentnone oxime or mineral acid salt thereof with liquid perature in step (a) is maintained at about 25] 25C. sulfur dioxide containing at least about 1 mole suland the reaction pressure is about 0.3-50 atmospheres. fur trioxide per mole a-aminocycloalkanone oxime 8. The method of claim 1 wherein the liquid sulfur 7 until a two-phase system comprising a liquid S0 dioxide phase separated in step (b) is recycled to step phase and an insoluble lactam precursor phase is (a). formed; 

1. A METHOD FOR THE PRODUCTION OF AN A-AMINO-W-LACTAM OF THE FORMULA:
 2. The method of claim 1 wherein the lactam precursor is neutralized and hydrolyzed simultaneously using an aqueous solution of ammonium sulfate and ammonia.
 3. The method of claim 1 wherein about 1.5-2.5 moles sulfur trioxide are present per mole Alpha -aminocycloalkanone oxime.
 4. The method of claim 1 wherein about 2 to 20 moles sulfur dioxide are present per mole sulfur trioxide.
 5. The method of claim 1 wherein the Alpha -aminocycloalkanone oxime is present in the form of its hydrochloride salt.
 6. THE METHOD OF CLAIM 1 WHEREIN THE A-AMINOCYCLOALKANONE OXIME IS A-AMINOCYCLOHEXANONE OXIME.
 7. The method of claim 1 wherein the reaction temperature in step (a) is maintained at about 25*-125*C. and the reaction pressure is about 0.3-50 atmospheres.
 8. The method of claim 1 wherein the liquid sulfur dioxide phase separated in step (b) is recycled to step (a). 